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Introduction Parental predisposition and age of onset may be independently associated with 1-year total weight loss (TWL) failure ( Methods This cohort study includes all cases of the German StuDoQ|MBE register (2015–2019) with data on parental predisposition, obesity onset, and at least 1-year follow up after primary MBS procedures (n = 14,404). We provide descriptive statistics of the cohort in terms of the main outcome and 1-year TWL failure, and provide characteristics of surgery type subgroups. Finally, we provide a multivariate logistic regression model of 1-year TWL failure. Results 58.8% and 45.7% of patients reported maternal and paternal predisposition for obesity, respectively. Average onset of obesity was 15.5 years and duration of disease 28.3 years prior to MBS. SG is the most frequently performed procedure (47.2%) followed by RYGB (39.7%) and OAGB (13.1%). Mean 1-year TWL is 32.7 ± 9.3%, and 7.8% (n = 1,119) of patients show TWL failure (p Conclusion The proportions of MBS patients that report on paternal and maternal predisposition for obesity are 45.7% and 58.8% respectively, and average age at onset is 15.5 years. 7.8% of patients do not meet current target criteria of successful response to surgery at 1 year. Early onset, male sex, age at operation, pre-operative BMI, pre-operative weight loss, SG, and T2D are independently associated with weight loss failure. Graphical abstract

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps . Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer(1,2). The accumulation of metabolites leads to cell stress and inflammation in the liver(3), but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology. We detected the hepatic accumulation of CD8 T cells with phenotypes that combined tissue residency (CXCR6) with effector (granzyme) and exhaustion (PD1) characteristics. Liver CXCR6(+) CD8 T cells were characterized by low activity of the FOXO1 transcription factor, and were abundant in NASH mice and in patients with NASH. Mechanistically, IL-15 induced FOXO1 downregulation and CXCR6 upregulation, which together rendered liver-resident CXCR6(+) CD8 T cells susceptible to metabolic stimuli (including acetate and extracellular ATP) and collectively triggered auto-aggression. CXCR6(+) CD8 T cells from the livers of NASH mice or of patients with NASH had similar transcriptional signatures, and showed auto-aggressive killing of cells in an MHC-class-I-independent fashion after signalling through P2X7 purinergic receptors. This killing by auto-aggressive CD8 T cells fundamentally differed from that by antigen-specific cells, which mechanistically distinguishes auto-aggressive and protective T cell immunity.

Obesity is a complex disease influenced by genetics, epigenetics, the environment, and their interactions. Mature adipocytes represent the major cell type in white adipose tissue. Understanding how adipocytes function and respond to (epi)genetic and environmental signals is essential for identifying the cause(s) of obesity. RNA and chromatin have previously been isolated from adipocytes using enzymatic digestion. In addition, protocols have been developed for nuclear isolation, where purification is achieved by fluorescence-activated cell sorting (FACS) of adipocyte-specific transgenic reporters. One of the greatest challenges to achieving high yield and quality during such protocols is the substantial amount of lipid contained in adipose tissue. The present protocol describes an optimized procedure for isolating mature adipocytes that leverages heptane to separate lipids from the targets of interest (RNA/chromatin). The resulting RNA has high integrity and generates high-quality RNA-seq results. Likewise, the procedure improves nuclei yield rate and generates reproducible ChIP-seq results across samples. Therefore, the current study provides a reliable and universal murine adipocyte isolation protocol suitable for whole-genome transcriptome and epigenome studies.

Objective The aim of this study was to compare silicone-banded sleeve gastrectomy (BSG) to nonbanded sleeve gastrectomy (SG) regarding weight loss, obesity-related comorbidities, and complications. Summary background data As a primary bariatric procedure, SG leads to excellent weight loss, yet weight regain is a relevant issue in mid- to long-term follow-up. Retrospective analyses suggest that banding a sleeve using a silicone ring may decrease weight regain and improve weight loss. Methods The banded versus nonbanded sleeve gastrectomy single-center, randomized controlled trial was conducted from January 2015 to August 2019. The primary endpoint was defined as excess weight loss 3 years after surgery. Secondary endpoints included the surgery's impact on obesity-related comorbidities, quality of life, and complications. The study was registered under DRKS00007729. Results Among 94 patients randomized, 97% completed 3-year follow-up. Mean initial body mass index was 50.9 kg/m [95% confidence interval (CI), 49.6-52.2]. Mean adjusted excess weight loss 3 years after SG amounted to 62.3% (95% CI, 56.2-68.5) and 73.9% ( 95% CI, 67.8-80.0) after BSG (difference 11.6%, P = 0.0073). Remission of type 2 diabetes occurred in 66.7% (4/6) after SG and in 91.0% (10/11) following BSG (P = 0.21). Three years after surgery, ring implantation correlated with decreased frequency of symptomatic reflux episodes (P = 0.01) but increased frequency of regurgitation (P = 0.03). The rate of major complications was not different between the study groups (BSG, n = 3; SG, n = 2; P = 0.63). Quality of life was better following BSG (P = 0.001). Conclusions BSG provided better weight loss than nonbanded SG 3 years after surgery. Regurgitation was the main clinically relevant negative effect after BSG.

Background In 2017, the prevalence of obesity (BMI ≥ 30 kg/m2) in Germany was approximately 16%. Obesity increases an individual's risk of developing type 2 diabetes (T2DM) and arterial hypertension; it also increases overall mortality. Consequently, effective treatment is a necessity. Approximately 20 000 bariatric operations are performed in Germany each year. Methods This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane databases and on current German clinical practice guidelines. Results The types of obesity surgery most commonly performed in Germany, Roux-en-Y gastric bypass and sleeve gastrectomy, lead to an excess weight loss of 27-69% ≥ 10 years after the procedure. In obese patients with T2DM, the diabetes remission rate ≥ 10 years after these procedures ranges from 25% to 62%. Adjusted regression analyses of data from large registries have shown that the incidence of malignancies is 33% lower in persons who have undergone obesity surgery compared to control subjects with obesity (unadjusted incidence 5.6 versus 9.0 cases per 1000 person-years). The operation can cause vitamin deficiency, surgical complications, gastroesophageal reflux, and dumping syndrome. Therefore, lifelong follow-up is necessary. Conclusion In view of an increasing number of patients undergoing bariatric surgery, it will probably not be feasible in the future for lifelong follow-up to be provided exclusively in specialized centers.

Background Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas. Materials and Methods We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness. Results DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham. Conclusion In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis. Graphical abstract

Background Laparoscopic sleeve gastrectomy (SG) achieves excellent weight loss, yet recent reports indicate weight regain in a substantial number of patients. Objectives Inserting a nonadjustable gastric band may improve weight loss after SG. Setting University Hospital, Germany. Methods In a retrospective matched-pair analysis 51 patients who underwent banded SG (BSG) using a silicone ring between November 2010 and May 2017 were compared with patients who underwent conventional SG regarding weight loss, complications, and co-morbidity. Median follow-up was 5 years. Results Total weight loss was equal in the early follow-up (P = .118 and P = .111) but significantly better in BSG 3 and 5 years after surgery (BSG versus SG at 3 yr 38.7% ± 7.8, n = 33 versus 31.9 ± 10.7, n = 33, P = .002; BSG versus SG at 5 yr 37.6% ± 8.5, n = 27 versus 29.5 ± 12.9, n = 23, P = .008). Ring placement had no significant impact on clinical reflux signs (Fisher's exact test P > .999), yet 37 % of BSG patients reported ≥1 regurgitation per week (Fisher's exact test P = .013, odds ratio 12.4). Conclusion BSG leads to better weight loss than nonbanded SG 5 years after surgery. This comes at the expense of a higher rate of regurgitation. At a time in which weight loss limitations of a stand-alone SG are becoming a clinical problem, banding the sleeve may be a strategy to improve weight loss with this procedure.

The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus. Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly. In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups. This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.

Background Bio‐absorbable sealants are widely used to reduce the rate and severity of postoperative pancreatic fistulas after distal pancreatectomy. However, numerous clinical trials have failed to demonstrate their clinical benefit. We therefore investigated stability and bio‐compatibility of absorbable sealants in vitro and in vivo. Methods In vitro, polymerized compounds were incubated in pancreatic juice before their stability was tested. In vivo, two compounds were used to seal the pancreatic stump after distal pancreatectomy in nine pigs. Burst pressure of the pancreatic stump, surgical outcome, histology of the pancreatic stump, systemic inflammation, and drain fluid was examined. Results Products based on fibrin or collagen were unstable in the presence of active pancreatic enzymes and completely dissolved within 2 h. Sealants using chemical cross‐linking of proteins showed improved stability for 7 days. In vivo, application of polyethylenglycol‐based sealant leads to complete closure of the pancreatic duct after 5 days, while a glutaraldehyde‐based sealant prevented physiological closure of the pancreatic main duct. Conclusions Many compounds used clinically to reinforce the pancreatic stump after distal pancreatectomy are inadequate due to instability in the presence of pancreatic enzymes. While selected bio‐absorbable sealants inhibited the natural healing of the pancreatic stump, polyethylenglycol‐based sealants should be tested in further clinical trials.

Introduction: Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. Material and Methods: In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10–18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. Results: Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6–25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, p < 0.0001 and p = 0.0001; baseline vs. 2nd follow-up, p < 0.0001 and p = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control p > 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, p = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, p = 0.43). Conclusion: SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Objective To examine pasireotide’s effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. Material and methods Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. Results Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. Conclusion Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Die chirurgische Therapie der Adipositas in Deutschland ist ein sich rasch entwickelndes Gebiet, welches streng an die Nationalen Leitlinien gebunden ist. Darstellung der Belastung der Adipositaszentren durch den exponentiellen Anstieg postbariatrischer Patienten In einer retrospektiven Studie haben wir deskriptiv die Entwicklung der ambulanten Patientenzahlen an unserem universitaren Adipositaszentrum (gegrundet 2007) untersucht. Die Patientenbesuche wurden jahrlich ausgewertet und in zwei Gruppen eingeteilt: Erstvorstellung und Wiedervorstellung. Die Anzahl der durchgefuhrten bariatrischen Operationen sowie deren Akzeptanz/Kostenubernahme durch die Krankenkassen wurden ebenfalls evaluiert. Im Jahr 2007 wurden insgesamt 318 Patienten gesehen: 156 waren Erstvorstellungen, 162 Wiedervorstellungen. Die Ablehnungsrate der Kostenubernahme durch die Krankenkassen betrug 16,8 %. 2016 gab es 1691 Patientenvorstellungen (2016 vs. 2007 + 532 %), hiervon 487 Erstvorstellungen (+312 %) und 1204 Wiedervorstellungen (+743 %). Die Ablehnungsrate seitens der Krankenkassen fiel auf 1,8 %, wahrend sich die Anzahl der Operationen nahezu verzehnfachte. Mit der steigenden Akzeptanz der bariatrischen Therapie muss sich eine vergleichsweise kleine Zahl an spezialisierten Zentren mit der exponentiell steigenden Nachsorgefrequenz auseinandersetzen. In Anbetracht des Ausmases der Adipositasepidemie stellt insbesondere eine adaquate Nachsorge ein soziookonomisches Problem dar, welches nur im interdisziplinaren Setting unter struktureller Integration in das komplexe Gesundheitssystem gelost werden kann.

Background Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. Methods We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca2+) channels in heterologous expression systems were used to determine the modulation of Ca2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. Results SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. Conclusions These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression.

There is an ongoing debate on which procedure provides the best treatment for type 2 diabetes. Furthermore, the pathomechanisms of diabetes improvement of partly anatomically differing operations is not fully understood. A loop duodenojejunostomy (DJOS) with exclusion of one third of intestinal length, a sleeve gastrectomy (SG), or a combination of DJOS + SG was performed in 8-week-old male ZDF rats. One, three, and six months after surgery, an oral glucose tolerance test and measurements of GLP-1, GIP, insulin, and bile acids were conducted. After an initial (4 weeks) equal glucose control, DJOS and DJOS + SG showed significantly lower glucose levels than SG 3 and 6 months after surgery. There was sharp decline of insulin levels in SG animals over time, whereas insulin levels in DJOS and DJOS + SG were preserved. GIP levels were significantly larger in both groups containing a sleeve at all three time points, whereas GLP-1 was equal in all groups at all time. Bile acid levels were significantly higher in the DJOS compared to the SG group at all time points. Interestingly, the additional SG in the DJOS + SG group led to lower bile acid levels 1 and 6 months postoperatively. The effect of SG on glucose control was transient, whereas a duodenal exclusion was the more effective procedure in this model due to a sustained pancreatic function with a preserved insulin secretion.

Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition.Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6 months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted. Body weight was documented weekly.DJOS and DiOS animals showed significantly better glucose control in all OGTTs than the SHAM group (two-way ANOVA p 0.0001). Body weight developed largely parallel in both intervention groups; SHAM animals had gained significantly less weight after 6 months (Mann-Whitney DJOS/DiOS vs. SHAM p 0.05, DJOS vs. DiOS p 0.05). Operative interventions had no impact on GLP-1 and GIP levels at any time point (Mann-Whitney p 0.05 for all). DJOS/DiOS operations could preserve insulin production up to 6 months, while there was already a sharp decline of insulin levels in the SHAM group (Mann-Whitney: DJOS/DiOS vs. SHAM p 0.05 for all time points). Additionally, insulin sensitivity was improved significantly 1 month postoperative in both intervention groups compared to SHAM (Mann-Whitney DJOS/DiOS vs. SHAM p 0.05).The data of the current study demonstrate a sharp amelioration of glucose control after duodenal exclusion with unchanged levels of GLP-1 and GIP. Direct or delayed hindgut stimulation had no impact on glucose control in our model.

Background Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. Materials and methods Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. Results Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. Conclusions RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.

Bariatrische Operationen werden in Deutschland immer haufiger durchgefuhrt. Primareingriffe werden meist in spezialisierten Zentren durchgefuhrt. Es gibt jedoch spate Komplikationen, die Monate bis Jahre nach der Operation auftreten und mit denen jeder Allgemein- und Viszeralchirurg, unabhangig von der Grose und Spezialisierung seiner Klinik, konfrontiert werden kann. Der laparoskopische Roux-Y-Magenbypass ist weltweit die am haufigsten durchgefuhrte bariatrische Operation. Durch das antekolische Hochfuhren der alimentaren Schlinge zum Pouch entsteht dorsal der alimentaren Schlinge und unterhalb des Kolon transversum eine Mesenteriallucke, auch Petersen-Lucke genannt. Sowohl hier als auch im Bereich der Mesenteriallucke der Roux-Anastomose kann es zu einer inneren Hernie kommen, d. h. der Dunndarm kann sich hier um die eigene Achse drehen. Abdominelle Beschwerden durch Darmobstruktion sind unspezifisch, aber sehr ausgepragt. Patienten prasentieren klinisch entweder ein akutes Abdomen oder intermittierende abdominelle, unspezifische Schmerzen mit Ubelkeit und selten auch Erbrechen. Meistens zeigen die klinischen und die laborchemischen Untersuchungen keinen wegweisenden Befund. Im Zweifel bildet daher die kontrastmittelverstarkte Computertomografie des Abdomens die bildgebende Diagnostik der Wahl. Eine diagnostische Laparoskopie sollte bei jedem Patienten mit klinischem Verdacht auf eine innere Hernie auch bei unauffalligem CT erfolgen. Die diagnostische Laparoskopie sollte durch einen laparoskopisch versierten Operateur mit Erfahrung in der bariatrischen Chirurgie durchgefuhrt werden, da ohne genaue Kenntnis der Bruchpforten die Zuordnung der Darmschlingen sehr schwierig ist. Der primare Blick geht nach inframesokolisch unter Hochheben des Kolon transversum. Von hier aus bietet sich bei offener Petersen-Lucke die direkte Sicht von rechts auf das Treitz-Band. Falls man rechts davon Dunndarm vorfindet, besteht eine Petersen-Hernie. Nach dem inframesokolischen Blick sollte man die Gastroenterostomie aufsuchen und sich entlang der alimentaren Schlinge nach distal in Richtung Jejunojejunostomie vorarbeiten. Dort findet man die 2. mogliche Lucke. Nachdem beide Lucken aufgefunden und ggf. eine Hernie reponiert werden konnte, sollten die Lucken mit einer nicht resorbierbaren Naht verschlossen werden.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p 0.001). Patients with3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS G12V mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.

Laparoscopic sleeve gastrectomy (LSG) can achieve excellent weight loss, yet sleeve dilatation with concomitant weight regain proves to be a relevant issue. Hence, additional restriction might improve results after LSG. In a retrospective matched-pair analysis, 42 patients who underwent banded LSG (BLSG) using a MiniMizer® ring between January 2012 and October 2014 were analysed regarding weight loss, complications and comorbidity. Median follow-up was 3 years. Forty-two patients who had undergone conventional LSG were selected as matched pairs. Mean preoperative BMI was 54.93 ± 7.42 kg/m2 for BLSG and 53.46 ± 6.69 kg/m2 for LSG (Mann-Whitney P = 0.540). Total weight loss (%TWL) was significantly greater in the BLSG group 3 years after surgery (BLSG 38.22% ± 7.26; n = 26 vs. LSG 32.69 ± 9.47; n = 26; P = 0.0154). Ring placement had no relevant impact on new-onset reflux (Fisher’s exact test P = 1.0) but a tendency towards reflux improvement when reflux pre-existed (odds ratio 1.96). The major side effect of ring implantation was regurgitation with over 44% of patients presenting with regurgitation >1 per week (Fisher’s exact test P = 0.0019, odds ratio 18.07). BLSG is a safe procedure showing similar comorbidity to conventional LSG. However, BLSG leads to a higher rate of postoperative regurgitation. Weight loss is significantly improved 3 years after surgery. Hence, additional ring implantation might be an option for increased restriction in LSG surgery.

Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51–19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13–12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25–14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12–14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29–3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13–2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13–2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21–5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04–2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

To investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.Sterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10(8) CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS.Moxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10(7) ± 2.4·10(7) vs. AN 4.9·10(4) ± 2.6·10(4) CFU/g; p 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis.In the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.

Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity.A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured.No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 μg/g) was lower by trend (p = 0.072) than in G1 (51.7 μg/g) and G2 (46.4 μg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml).A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.

OBJECTIVE Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice. METHODS Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 10 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed. RESULTS Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis. CONCLUSIONS Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice.

It has been shown that crystalloid fluid-overload promotes anastomotic instability. As physiologic anastomotic healing requires the sequential infiltration of different cells, we hypothesized this to be altered by liberal fluid regimes and performed a histomorphological analysis.36 Wistar rats were randomized into 4 groups (n=8-10 rats/group) and treated with either liberal (+) or restrictive (-) perioperative crystalline (Jonosteril = Cry) or colloidal fluid (Voluven = Col). Anastomotic samples were obtained on postoperative day 4, routinely stained and histophathologically reviewed. Anastomotic healing was assessed using a semiquantitative score, assessing inflammatory cells, anastomotic repair and collagenase activity.Overall, the crystalloid overload group (Cry (+)) showed the worst healing score (P0.01). A substantial increase of lymphocytes and macrophages was found in this group compared to the other three (P0.01). Both groups that received colloidal fluid (Col (+) and Col (-)) as well as the group that received restricted crystalloid fluid resuscitation (Cry (-)) had better intestinal healing. Collagenase activity was significantly higher in the Cry (+) group.Intraoperative infusion of high-volume crystalloid fluid leads to a pathological anastomotic inflammatory response with a marked infiltration of leukocytes and macrophages resulting in accelerated collagenolysis.

Background Therapy for systemic complications in severe necrotizing pancreatitis remains symptomatic owing to the unavailability of more specific therapeutic targets. We investigated the differential gene expression in typically affected organs in a mouse model of severe necrotizing pancreatitis. Methods Acute necrotizing pancreatitis was induced in mice by retrograde infusion of taurocholate into the common bile duct. Microarray hybridization was subsequently performed with mRNA isolated from the spleen, liver, intestine, and lungs. Additionally, quantitative real-time polymerase chain reaction was performed to confirm the microarray results. Results Severe necrotizing pancreatitis induced widespread changes in gene expression, affecting 27.20% of the genes tested in the spleen and 29.07% in the liver. Fewer genes were differentially regulated in the intestine (10.28%) and the lungs (10.75%). Only 10 genes were found to be upregulated in all 4 organs using microarray analysis. This upregulation in all organs was confirmed by quantitative real-time polymerase chain reaction for only 3 molecules. These molecules were lipocalin 2, insulin-like growth factor binding protein 1, and CD14. Additionally we observed significantly aberrant gene regulation of inter-α-trypsin inhibitor family members in several organs. Conclusions Differential gene regulation in severe necrotizing pancreatitis is far more organ specific than anticipated, with only 3 molecules uniformly regulated systemically. The inter-α-trypsin inhibitor family of molecules appears to play a crucial biologic role in the systemic inflammatory response in acute pancreatitis. Finally, owing to its regulation and function, α1-microglobulin (or bikunin) may be a suitable predictive marker of the systemic inflammatory response syndrome in acute pancreatitis.

BackgroundPatients with pancreatic carcinoma have a grim prognosis. Here, we examine the induction of an in vitro antibody response of human B cells to pancreatic carcinoma antigens.Material and methodsCells of five cultured pancreatic ductal adenocarcinoma lines were lysed and their plasma membrane fragments isolated in an aqueous two-phase-system. The plasma membrane fragments were then added to cultures of isolated peripheral blood mononuclear cells from healthy volunteers for 14 days to act as a tumor antigen. Also, we added combinations of IL-2, IL-4, IL-21, anti-CD40 mAb and varying protein concentrations of the plasma membrane fragments to these cultures. We then tested characteristics and binding of resulting IgG and IgM against aforementioned tumor plasma membrane fragments and their respective cells using ELISAs.ResultsThe combination of IL-2, IL-4 and anti-CD40 mAb elicited IgM production showing significant binding (p

Background Health professionals often manage medical problems in critical situations under time pressure and on the basis of vague information. In recent years, dual process theory has provided a framework of cognitive processes to assist students in developing clinical reasoning skills critical especially in surgery due to the high workload and the elevated stress levels. However, clinical reasoning skills can be observed only indirectly and the corresponding constructs are difficult to measure in order to assess student performance. The script concordance test has been established in this field. A number of studies suggest that the test delivers a valid assessment of clinical reasoning. However, different scoring methods have been suggested. They reflect different interpretations of the underlying construct. In this work we want to shed light on the theoretical framework of script theory and give an idea of script concordance testing. We constructed a script concordance test in the clinical context of “acute abdomen” and compared previously proposed scores with regard to their validity. Methods A test comprising 52 items in 18 clinical scenarios was developed, revised along the guidelines and administered to 56 4th and 5th year medical students at the end of a blended-learning seminar. We scored the answers using five different scoring methods (distance (2×), aggregate (2×), single best answer) and compared the scoring keys, the resulting final scores and Cronbach’s α after normalization of the raw scores. Results All scores except the single best answers calculation achieved acceptable reliability scores (>= 0.75), as measured by Cronbach’s α. Students were clearly distinguishable from the experts, whose results were set to a mean of 80 and SD of 5 by the normalization process. With the two aggregate scoring methods, the students’ means values were between 62.5 (AGGPEN) and 63.9 (AGG) equivalent to about three expert SD below the experts’ mean value (Cronbach’s α : 0.76 (AGGPEN) and 0.75 (AGG)). With the two distance scoring methods the students’ mean was between 62.8 (DMODE) and 66.8 (DMEAN) equivalent to about two expert SD below the experts’ mean value (Cronbach’s α: 0.77 (DMODE) and 0.79 (DMEAN)). In this study the single best answer (SBA) scoring key yielded the worst psychometric results (Cronbach’s α: 0.68). Conclusion Assuming the psychometric properties of the script concordance test scores are valid, then clinical reasoning skills can be measured reliably with different scoring keys in the SCT presented here. Psychometrically, the distance methods seem to be superior, wherein inherent statistical properties of the scales might play a significant role. For methodological reasons, the aggregate methods can also be used. Despite the limitations and complexity of the underlying scoring process and the calculation of reliability, we advocate for SCT because it allows a new perspective on the measurement and teaching of cognitive skills.

Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers.A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses).After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 μg/mL, NAP 267.2 ± 49.6 μg/mL; P0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P0.05), whereas monocytes increased fourfold within 48 h (P0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen.Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes.

Objectives Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods. Methods Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA. Results In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE. Conclusions Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy.